Sialyltransferase Regulates Nervous System Function in Drosophila

作者：Elena Repnikova, Kate Koles, Michiko Nakamura, Jared D. Pitts, Haiwen Li, Apoorva Ambavane, Mark J. Zoran, Vladislav M. Panin · 发表于：Journal of Neuroscience · 年份：2010 · DOI：10.1523/jneurosci.5253-09.2010 · 被引用次数：77 · 研究领域：Invertebrate Immune Response Mechanisms、Glycosylation and Glycoproteins Research、Neurobiology and Insect Physiology Research

In vertebrates, sialylated glycans participate in a wide range of biological processes and affect the development and function of the nervous system. While the complexity of glycosylation and the functional redundancy among sialyltransferases provide obstacles for revealing biological roles of sialylation in mammals, Drosophila possesses a sole vertebrate-type sialyltransferase, Drosophila sialyltransferase (DSiaT), with significant homology to its mammalian counterparts, suggesting that Drosophila could be a suitable model to investigate the function of sialylation. To explore this possibility and investigate the role of sialylation in Drosophila, we inactivated DSiaT in vivo by gene targeting and analyzed phenotypes of DSiaT mutants using a combination of behavioral, immunolabeling, electrophysiological, and pharmacological approaches. Our experiments demonstrated that DSiaT expression is restricted to a subset of CNS neurons throughout development. We found that DSiaT mutations result in significantly decreased life span, locomotor abnormalities, temperature-sensitive paralysis, and defects of neuromuscular junctions. Our results indicate that DSiaT regulates neuronal excitability and affects the function of a voltage-gated sodium channel. Finally, we showed that sialyltransferase activity is required for DSiaT function in vivo, which suggests that DSiaT mutant phenotypes result from a defect in sialylation of N-glycans. This work provided the first evidence that sialylati...